rs73531153

Variant names:

• chrX-106821115-C-T
• rs73531153
• NM_017752.3:c.360+120C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017752.3(TBC1D8B):​c.360+120C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 400,985 control chromosomes in the GnomAD database, including 733 homozygotes. There are 2,406 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (550 hom., 1869 hem., cov: 22)
  • Exomes 𝑓: 0.0081 (183 hom. 537 hem.)
• Consequence: TBC1D8B NM_017752.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.633
• Publications: 0 publications found

Genes affected

TBC1D8B (HGNC:24715): (TBC1 domain family member 8B) This gene encodes a protein with a TBC (Tre-2/Bub2/CDC16) domain. Some mammalian proteins with this domain have been shown to function as Rab-GAPs by binding to specific Rab proteins and affecting their GTPase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

MORC4 (HGNC:23485): (MORC family CW-type zinc finger 4) In human, the four current members of the microrchidia (morc) gene family share an N-terminal ATPase-like ATP-binding region and a CW four-cysteine zinc-finger motif. The protein encoded by this gene also has a nuclear matrix binding domain and a two-stranded coiled-coil motif near its C-terminus. This gene is widely expressed at low levels in normal tissues and has elevated expression in placenta and testis. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-106821115-C-T is Benign according to our data. Variant chrX-106821115-C-T is described in ClinVar as [Benign]. Clinvar id is 1253489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D8B	NM_017752.3	c.360+120C>T		intron_variant	Intron 3 of 20	ENST00000357242.10	NP_060222.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D8B	ENST00000357242.10	c.360+120C>T		intron_variant	Intron 3 of 20	1	NM_017752.3	ENSP00000349781.5

Frequencies

GnomAD3 genomes AF: 0.0616 AC: 6816 AN: 110648 Hom.: 548 Cov.: 22

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0246

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00150

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00844

Gnomad NFE AF: 0.000569

Gnomad OTH AF: 0.0480

GnomAD4 exome AF: 0.00806 AC: 2341 AN: 290287 Hom.: 183 AF XY: 0.00668 AC XY: 537 AN XY: 80415

African (AFR) AF: 0.228 AC: 1713 AN: 7518

American (AMR) AF: 0.0142 AC: 157 AN: 11052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8471

East Asian (EAS) AF: 0.00 AC: 0 AN: 19903

South Asian (SAS) AF: 0.00116 AC: 17 AN: 14634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32545

Middle Eastern (MID) AF: 0.0110 AC: 26 AN: 2358

European-Non Finnish (NFE) AF: 0.000396 AC: 70 AN: 176567

Other (OTH) AF: 0.0208 AC: 358 AN: 17239

GnomAD4 genome AF: 0.0618 AC: 6840 AN: 110698 Hom.: 550 Cov.: 22 AF XY: 0.0564 AC XY: 1869 AN XY: 33120

African (AFR) AF: 0.213 AC: 6478 AN: 30404

American (AMR) AF: 0.0245 AC: 255 AN: 10397

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2631

East Asian (EAS) AF: 0.00 AC: 0 AN: 3517

South Asian (SAS) AF: 0.00113 AC: 3 AN: 2654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5960

Middle Eastern (MID) AF: 0.00930 AC: 2 AN: 215

European-Non Finnish (NFE) AF: 0.000569 AC: 30 AN: 52716

Other (OTH) AF: 0.0474 AC: 72 AN: 1518

Alfa AF: 0.0474 Hom.: 181

Bravo AF: 0.0717

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 22, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.74
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs73531153; hg19: chrX-106064345;